Objectives of the Amish Study are to examine questions about diagnostic, epidemiologic and genetic aspects of the bipolar (BP) and unipolar (UP) forms of affective disorders. The OLD ORDER AMISH, a human isolate, serves as an ideal type of research laboratory to identify homogeneous subtypes of affective illness and to test hypotheses on heritability. Data are available from multigenerational pedigrees with large sibships based on confirmed cases of BP and UP disorder. DIAGNOSTIC/EPIDEMIOLOGIC AIMS are: a) to develop full diagnostic data on extended pedigrees and to assess comparative morbid risks for BP/UP lines; b) to develop detailed clinical profiles on the BP patients focusing on the differences in age of onset, symptomatology and pedigree patterns; and c) to conduct prospective, longitudinal course of illness study for BP and UP patients using life table analyses. GENETIC AIMS are: a) to conduct pedigree and segregation analyses on a number of large, extended pedigrees (BP and UP) to estimate the likelihoods of different hypotheses regarding mode of inheritance (using PAP, GEMINI and GENPED) under a variety of diagnostic schemes; b) to support continued extensive linkage study on a wide variety of markers and the typing of subjects for restriction fragment polymorphisms (RFLP) performing genetic linkage analyses using LIPED, modified, and PAP with different diagnostic hierarchies; and c) to complete the Progenitor Trace Study for analysis of specific gene pathways from Amish ancestors to present day patients. The long term goal is identification of the subtypes of affective disorder as evidenced by clinical course, distinct modes of transmission and the possible confirmation of a genetic marker. This would advance our understanding of the genetics of affective disorders and aid in diagnosis and treatment.